Studies in NHE3 and AQP1 knockout mice, transport proteins in the proximal tubule of the kidney where 60-70% of the filtered Na is normally reabsorbed, have shown that these mice maintain a normal salt balance and that a reduction in glomerular filtration rate is the main compensatory mechanism preventing salt losses. The reduction in GFR is caused by a signal transmitted from the distal tubule to the glomerular arterioles across the juxtaglomerular apparatus. This mechanism, called the tubuloglomerular feedback (TGF) mechanism, has been found to be inoperative in mice with targeted deletion of the adenosine 1 receptor gene. Results obtained in this novel mouse strain strongly indicate that the local production of adenosine, acting through adenosine 1 receptors on afferent glomerular arterioles, is responsible for TGF mediated vasoconstriction. Adenosine 1 receptor knockout mice have an increased expression of renin suggesting that these receptors also mediate inhibition of renin synthesis. The availability of a mouse model lacking TGF regulation of GFR will greatly facilitate understanding the role of this regulatory mechanism in animals with transport defects and in other functional states. In mice deficient in cyclooxygenases 1 or 2 we have found that chronic inhibition of the NKCC2 transporter by the loop diuretic bumetanide causes an increase in NaCl excretion whose magnitude depends on the presence of prostaglandins generated by both COX-1 and COX-2, but that the stimulation of renin secretion, one of the compensatory responses to NKCC2 inhibition, was fully dependent on COX-2.